Emma Guymer

Rheumatologist Monash Medical Centre

Giant Cell Arteritis

Polymyalgia Rheumatica

Fibromyalgia
GCA / PMR Spectrum
Overlapping clinical phenotypes
• Classic cranial arteritis
• Extra cranial / Large vessel GCA
• Polymyalgia rheumatica

Manifestations of the same

pathophysiological spectrum
 GCA / PMR spectrum
• Occur in the same patient population, in people of 50 years
or older
• HLA-DRB1*04 IN Northern Europeans
• Polymorphisms in genes coding for cytokines, chemokines and adhesion
molecules
• Age-related changes in the immune system and vascular tissue

• Can occur separately, or together in the same patient:

• At same time
• At different times

• PMR 3–10 X more common than GCA

 GCA / PMR spectrum
• 40 - 60% GCA pts at diagnosis have PMR

• In patients with PMR and no arteritic symptoms

• 10 – 20% have temporal arteritic changes on biopsy
• 30% have vascular FDG uptake on PET scan

• At diagnosis 80% GCA and ~33% PMR pts have

subclinical LV inflammation on PET
Giant Cell Arteritis
 Giant Cell Arteritis (GCA)
• Also called Temporal Arteritis
• Most common primary vasculitis in
older persons
• Rare in pts < 50 years old
• Mostly white population 3F : 1M
• Medium-large vessel vasculitis
• Typically 2-3rd order branches of
proximal aorta
• especially those of the external
carotid artery

Francesco Giamberti
 Giant Cell Arteritis (GCA)
• Some familial aggregation also environmental factors

• Incidence, severity and risk of visual complications associated

with HLA-DRB1*04 alleles in Northern Europeans

• IL-17A, IL-33 polymorphisms associated with GCA (Marquez 2014)

• Scandinavian ancestry possible risk factor

• Current or ever-smokers small increased risk (Brennan 2018)

 IL-17 axis INF-γ axis

DC DC

IL-1β IL-12
IL-6 IL-18
IL-23

Th17 Th1
T cell T cell

IL-17 INF-γ

EC, VSMC Macrophages

Fibroblasts Endothelial cells
Bone marrow stromal cells Cytotoxic cells
Acute phase response

Steroid responsive Less steroid responsive

 Giant Cell Arteritis (GCA)
• Disturbed B cell homeostasis (van der Geest 2014)
• Number of B effector cells reduced in active disease but return to normal in
steroid-induced remission
• Recovery not due to compensatory hyperproliferation or enhanced bone-marrow
production ? redistributed to unidentified site during active disease
• Exaggerated production of IL-6 when they return

• Possible implication of VZ virus ? (Gliden 2016)

• Found in and around TAs of patients with GCA (+/- Bx) but also in 20% of
controls
• Needs to be replicated
 Giant Cell Arteritis (GCA)
• Mean age onset 70 years

• Dramatic or insidious onset

• Accounts for ~15% of pts > 65 yrs with PUO

• Occult malignancy can mimic Sx

• If poor response to steroid or general deterioration look for
malignancy
 Clinical Features of GCA

Manifestations Of Vascular Injury / Insufficiency

• Clinical features relate to affected arteries
Headache
• Most common symptom (>67% pts)
• Begins early – often presenting symptom
• Severe, usually localised to the temple
• May be occipital or less defined
• May be precipitated by brushing hair
• Can subside even when disease is still active
 Clinical Features of GCA
Jaw claudication
• Relatively specific for GCA

CNS ischaemia, TIAs or stroke

• Stenotic lesions in vertebral or basilar arteries

Scalp tenderness
• Particularly around temporal and occipital arteries
 Clinical Features of GCA

Tongue claudication

Sore throat or painful swallowing

Peripheral neuropathies
Arteries can be thickened, tender and nodular, with
reduced or absent pulsation
N Engl J Med
2018;
378:2517
 Clinical Features of GCA

Visual disturbances in 25 – 50%

• Incidence of visual loss 10 - 15 %

• Usually sudden, painless and permanent
• Usually ant / post ischaemic optic neuropathy
• Other
• Amaurosis fugax
• retinal ischaemia
• diplopia
 Clinical Features of GCA

Involvement of other arteries

• Aorta and major branches in ~ 25%
• CTA, MRA, PET

• Coronaries (MI, AR, CCF)

• Clinical evidence of large artery involvement

• Bruits / tenderness over arteries
• Limb claudication / ischaemia
• Absent / asymmetrical pulses
• Aortic dissection and rupture – often a late complication
 CTA and MRA of the Aortic Arch in Two Patients with Giant-Cell Arteritis.

Weyand CM, Goronzy JJ. N Engl J Med 2014;371:50-57.

 Clinical Features of GCA
Manifestations of Systemic Inflammation
Polymyalgia rheumatica
• Stiffness & pain in muscles of shoulders, pelvic girdle and neck;
rarely torso

Constitutional symptoms
• Anorexia, weight loss, fever, malaise, night sweats, depression,
fatigue

Peripheral synovitis
• Mostly wrists
 Investigations in GCA
ESR & CRP
• usually elevated (useful to monitor Rx)
• Can be normal (but very rarely)
IL-6 & B cell Activating Factor (BAFF)
• usually elevated, found to correlate with ESR/CRP
Anaemia (Normochronic or hypochromic)
Thrombocytosis
SPEP
• Non-spec increase in some globulins
 Investigations in GCA

Thyroid abnormalities
• Assoc. with thyrotoxicosis – generally follows
hyperthyroidism, sometimes hypothyroidism

Liver abnormalities
• Abn LFTS common (ALP and GGT)

Anti-cardiolipin Ab in some
 Investigations in GCA

Temporal Artery Biopsy

• High false negative rate
• 1/3 of patients with clinical signs and Sx
• Higher likelihood with longer Rx with steroid
• Can have non-specific changes esp. after Rx

• Need ~ 2 cm length
• Value of having positive histology for later on when
making treatment decisions
• Occas. involvement of TA in other vasculitides, esp PAN
 Investigations in GCA

Histopathology
• Muscular arteries with well developed elastic
laminae and vasa vasorum
• Superficial temporal, vertebral, opthalmic and posterior
ciliary arteries

• Less severe involvement in carotids and central retinal

arteries

• Intracranial vessels seldom involved

 Investigations in GCA
Histopathology
• Panarteritis – lymphocytes (CD4+ T cells), histiocytes
& plasma cells
• Giant-cell granulomas (not always seen)
• Disruption of internal elastic lamina
• Can also be caused by aging or atheroma
• Will be visible long term regardless of previous steroid
treatment
• Patchy & skip lesions
• Vessels can be thrombosed or stenosed with
inflammatory vessel wall thickening
 Investigations in GCA
Colour doppler ultrasound of cranial arteries
• Non-invasive assessment of the superficial arteries
(bilateral temporal and occipital a.)
• Looking for hypoechoic wall thickening (halo) caused by
oedema (sens 77%, spec 96%) esp if non-compressible
• Operator dependent
• Particularly useful in certain situations:
• As a guide for biopsy site
• Unable to biopsy
• Past negative biopsy with flare
• Now being considered as first line Ix in patients with high
clinical likelihood in experienced centres
Duftner et al 2018
 Investigations in GCA

High-resolution MRI of superficial cranial arteries

• Also non- invasive
• More expensive, less widely available
• Less operator dependant
• Can assess extra-cranial involvement in same study
• Sensitivity 73% and specificity 88%

Duftner et al 2018
Figure 1. Representative findings with each imaging approach in a case of biopsy-
proven giant cell (temporal) arteritis. A, Magnetic resonance image (MRI). Mural
thickening and contrast enhancement in the superficial temporal artery are seen in
the enlarged MRI (arrow). The central black lumen of the artery is due to the flow
void of fast-moving spins, compared with the lack of a flow void of slower-moving
spins in the concomitant vein (arrowhead). B, Color-coded duplex sonogram
(CCDS). The dark concentric halo (arrow) is the characteristic imaging finding in
CCDS
EULAR recommendations for the use of
imaging in LVV in clinical practice
Dejaco et al 2018

1. In patients with suspected GCA, an early imaging test is recommended to complement the clinical
criteria for diagnosing GCA, assuming high expertise and prompt availability of the imaging
technique. Imaging should not delay initiation of treatment.
2. In patients in whom there is a high clinical suspicion of GCA and a positive imaging test, the
diagnosis of GCA may be made without an additional test (biopsy or further imaging). In patients
with a low clinical probability and a negative imaging result, the diagnosis of GCA can be
considered unlikely.
3. Ultrasound of temporal±axillary arteries is recommended as the first imaging modality in patients
with suspected predominantly cranial GCA. A non-compressible ‘halo’ sign is the ultrasound
finding most suggestive of GCA.
4. High resolution MRI of cranial arteries to investigate mural inflammation may be used as an
alternative for GCA diagnosis if ultrasound is not available or inconclusive.
5. CT and PET are not recommended for the assessment of inflammation of cranial arteries.
6. Ultrasound, PET, MRI and/or CT may be used for detection of mural inflammation and/or luminal
changes in extracranial arteries to support the diagnosis of LV-GCA. Ultrasound is of limited value
for assessment of aortitis.
 EULAR recommendations for the use of
imaging in LVV in clinical practice
Cont’d

7. In patients with suspected TAK, MRI to investigate mural inflammation and/or luminal changes
should be used as the first imaging test to make a diagnosis of TAK, assuming high expertise and
prompt availability of the technique.
8. PET, CT and/or ultrasound may be used as alternative imaging modalities in patients with
suspected TAK. Ultrasound is of limited value for assessment of the thoracic aorta.
9. Conventional angiography is not recommended for the diagnosis of GCA or TAK as it has been
superseded by the previously mentioned imaging modalities.
10. In patients with LVV (GCA or TAK) in whom a flare is suspected, imaging might be helpful to
confirm or exclude it. Imaging is not routinely recommended for patients in clinical and
biochemical remission.
11. In patients with LVV (GCA or TAK), MRA, CTA and/or ultrasound may be used for long-term
monitoring of structural damage, particularly to detect stenosis, occlusion, dilatation and/or
aneurysms. The frequency of screening as well as the imaging method applied should be decided
on an individual basis.
12. imaging examination should be done by a trained specialist using appropriate equipment,
operational procedures and settings. The reliability of imaging, which has often been a concern,
can be improved by specific training.
 Investigations in GCA
Assessment of extra-cranial, large vessel involvement
• CTA & MRA useful, however some changes are not reversible, so can’t
be used to monitor inflammatory burden or disease activity
• Angiography

• PET scanning -can detect inflammation in extracranial large vessels

• Not useful in evaluating temporal arteries (too small, & high activity in
nearby brain)
• ? Lower limb false positives linked to atheroma
• PET-CT of TA, MA and VAs
• Sens 82% & spec 100% in single retrosp, case control study. Steroid naive
• ? Useful in monitoring inflammatory burden – no data Nielsen 2018
PET
 Giant Cell Arteritis (GCA)
ACR 1990 Classification Criteria for GCA (3 of 5)
• Age at disease onset ≥ 50yrs
• Headache of new onset or new type
• Tenderness or reduced pulsation of TA
• Elevated ESR (≥ 50 mm/hr)
• Histological changes of arteritis (either granulomatous
lesions, usually with multinucleated giant cells, or diffuse
mononuclear cell infiltration)
 Management of GCA
Steroid
• Mainstay of therapy
• Rapid response
• Reduction in complication incidence incl. blindness
• Preferably given after biopsy BUT commence Rx if
strong suspicion or visual symptoms even if biopsy is
delayed
• Use even if Bx is negative if strong clinical suspicion

BLINDNESS CAN OCCUR AT ANY TIME BEFORE

TREATMENT
 Management of GCA
Steroids (cont’d)
• Pulse IV methylpred. or high dose oral if visual symptoms
• Less if no visual Sx (~ 1mg/kg o pred)
• Slow taper once symptoms controlled (~ 1m)
• Gradual reductions at lower doses (when <10mg/d then taper
1mg/month)
• Rapid reduction/withdrawal can lead to relapse
• Usually on steroid for ~ 2 years
• Watch for relapse at low steroid doses or after cessation
• May need steroid sparing agents (eg MTX, leflunomide)
REMEMBER BONES & other steroid complications incl. Pneumocystis
jirovecii pneumonia prophylaxis
 Management of GCA
• Consider aspirin and proton pump inhibitor

• ? ARB helpful to prevent relapse - needs further study (Alba 2014)

• Trials

• Tocilizumab and sirukumab (anti IL-6 R Abs), anakinra (IL-1RA), and gevokizumab (IL-1 blockade)
target IL17 pathway

• Ustekinumab (IL-12 & 23 Ab) and abatacept (CD 28 costim. inhib.) target both IL 17 and INF γ
pathways

• Baricitinib (targets JAK1 & JAK2)

• Good prognosis with many patients off treatment by 5yrs

• Monitoring CXR & inflammatory markers every 2 years

 GiACTA trial – 1 year data
Stone JH, et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med 2017;377(4):317-28

• RDBPC phase III trial of tocilizumab (IL-6r inhibitor) in GCA

• Tocilizumab + 26 week PNL taper was superior to 26 or 52
week PNL taper + placebo WRT sustained GCA remission
• Greater disease control with toci weekly vs. fortnightly
• Tocilizumab was associated with reduced cumulative PNL
dose over 52 weeks
• Tocilizumab was associated with fewer serious adverse
events
• Infection most commonly reported AE across all groups
• Await 2 year data for durability of remission and safety
 GCA - Summary
• Most common vasculitis in people over 50yrs
• Clinical features relate to vascular injury and systemic
inflammation
• Obtain histological confirmation in all patients if possible,
but should not delay starting treatment
• Extremely sensitive to corticosteroid
• Closely linked to polymyalgia rheumatica
Polymyalgia
Rheumatica
 Polymyalgia Rheumatica (PMR)
Clinical syndrome of aching pain and stiffness in
the neck, shoulder and pelvic girdles

• Rare in patients < 50 yrs (mean onset 70yrs)

•F > M Lifetime risk: F=2.43%; M=1.66%
• Dramatic or insidious onset
• Assoc. with HLA class II genes
• Varies with geographic regions
 IL-17 axis INF-γ axis

DC DC

IL-1β IL-12
IL-6 IL-18
IL-23

Th17 Th1
T cell T cell

IL-17 INF-γ

EC, VSMC Macrophages

Fibroblasts Endothelial cells
Bone marrow stromal cells Cytotoxic cells
Acute phase response

Steroid responsive Less steroid responsive

 Clinical Features of PMR
Musculoskeletal symptoms
• Pain and stiffness
• Shoulder region & neck → shoulder & pelvic girdles → proximal
muscles
• Usually bilateral and symmetric
• Stiffness particularly severe after rest & in mornings
• Pain worse with movement and night / early am
• Muscle strength normal but difficult to test
• Tenderness
• Later → muscle atrophy
 Clinical Features of PMR
Tenosynovitis & Synovitis
• Tenosynovitis/bursitis of shoulder, hip
• ? responsible for pain and stiffness
• Mild inflammatory synovitis and effusions
• Knees, wrists and more proximal joints incl. sternoclavicular joints

• Carpal tunnel syndrome

• Distal pitting oedema (extensive underlying tenosynovitis)

 Clinical Features of PMR
Constitutional symptoms:
• Low–grade fever
• Fatigue
• Anorexia
• Weight loss
• Malaise
• Depression
 Clinical Features of PMR
PMR can mimic many other conditions:
• Can have PMR-type symptoms at onset of RA in
elderly
• 20% of pts presenting with PMR-type symptoms will have
developed RA after 1 year
• Myositis
• In myositis weakness limits function
• In PMR pain limits function
• Paraneoplastic myalgias
• Connective Tissue Diseases
 Investigations in PMR
• Raised ESR & IL-6
• Anaemia
• Increased immunoglobulins
• Abn. LFTs (ALP & GGT)
• non- spec. inflam. On Bx
• Normal muscle enzymes / normal EMG / some atrophy, no
inflammation on Bx
• Non-spec. inflam. synovial fluid
 Investigations in PMR
Imaging
• ultrasound or MRI – peri >>intra articular inflammation
• Subacromial, subdeltoid, trochanteric and cervical bursitis
• Tenosynovitis of long biceps head
• Mild Glenohumeral or hip synovitis
• FDG PET/CT
• Can help with atypical presentations
• Interspinous bursitis, widespread enthesopathy and periarticular
inflammation (particularly volar surfaces of hands, gr. trochanters,
shoulders & hips), synovitis +/- background med or large vessel vasculitis

• Beware peripheral synovitis – suggests an alternative diagnosis

eg. RA or inflammatory OA
 Investigations in PMR
Rule out Giant Cell Arteritis:
• When in doubt, biopsy!
• Findings of GCA (biopsy or imaging) together with clinical features
override PMR diagnosis
• Less clear significance of subclinical LV inflammation when
considering management (more studies needed)
• Sometimes can see small-vessel vasculitis surrounding an
uninflamed TA – significance unclear
 Provisional ACR-EULAR 2012
classification criteria for PMR
Mandatory
• Age ≥ 50 yrs
• Aching in both shoulders
• Abn. CRP and/or ESR

Additional (≥ 4 points without U/S or ≥ 5 points with U/S)

• Morning stiffness > 45 mins (2 points)
• Hip pain or  ROM (1 point)
• Negative Rh F or CCP Ab (2 points)
• No peripheral synovitis (1 point)
• Ultrasound findings in shoulders / hips (1-2 points)
 Management of PMR
Steroid
• Mainstay of treatment
• Rapid response
• Dose depends on if there is coexisting GCA
• If not, then 15 - 20mg o prednisolone per day
• Gradual reduction once symptoms controlled
• Need very slow wean at lower doses
• Average time of Rx is 2 years
At presentation

After one week of PNL 10mg/day

 Management of PMR
Watch for relapse at low steroid doses or after cessation
• May need steroid sparing agents (eg. MTX)
• Consider aspirin and proton pump inhibitor
• Watch for development of vasculitis
REMEMBER BONES & other steroid complications
• ? Future role for blockade of IL-6R
• Good prognosis with many patients off treatment by
5yrs
 PMR - Summary

• Syndrome of muscular pain, stiffness and constitutional

symptoms in patients over 50yrs

• Can mimic other conditions

• Closely linked to giant cell arteritis

• Extremely sensitive to corticosteroid

Fibromyalgia
 Fibromyalgia
Syndrome of chronic, widespread musculoskeletal pain &
tenderness
“Centralised Pain Syndrome”
or
“Central Sensitivity Syndrome”
• 2 - 4% population
• 10% of population reports chronic pain

• Occurs in more women than men

• Occurs alone or with other chronic disease
 Fibromyalgia diagnostic
threshold

Movement up or down the scale

depending on severity and response
to chronic stress

Central sensitivity levels

Start-point partially determined by genetics and response to previous experiences

 Fibromyalgia
Co-exists with other chronic illness
• 41% of RA pts and 22% of CCF pts met FM criteria
• associated with worse health outcomes (Gist 2013)

• 22% of SLE pts met FM criteria (Wolfe 2009)

• 30-40% of patients with autoimmune thyroid disease (Tagoe

2012)

• 18% of patients with type 2 DM (Yanmaz 2012)

 Fibromyalgia
Not damaging or degenerative, but high burden
• Significantly diminished personal health
• Self-rated quality of life lower than with RA, renal dialysis and
many other chronic diseases

• Wide-ranging downstream societal costs

• Health care costs
• Absenteeism / Underemployment / Unemployment
• Disability / sickness benefits
• Family & social network burdens
Why does fibromyalgia develop?
Genetically susceptible
• First-degree relatives of people with fibromyalgia are more likely to have
fibromyalgia or other chronic pain states
• Approximately 50% of the risk of developing fibromyalgia and related
conditions is genetic
• Many different gene polymorphisms are associated – most of these regulate
or modify the function of neurotransmitters in pain sensitivity pathways

Trigger stressor (physical / psychological) - in many patients

• Early life stressors
• Children born in 1958 who had experienced a motor traffic accident or who were institutionalized
were 1.5 – 2X more likely to have CWP 42 years later
• Peripheral pain syndromes (e.g. RA, SLE, osteoarthritis)
• Physical trauma (eg car accidents)
Post- military deployment
Clauw D, et al. Neuroimmun. 1997;4:134-153.
• McLean SA, et al. Med Hypoth. 2004;63:653-

Infections
658.
• Jones et. al. ACR 2007

Psychological stress/distress
Clauw et. al. JCR 1997.
• McBeth ACR 2006
Clauw et. al. J Occup Environ Med. 2003
Oct;45(10):1040-8.
Ablin et. al Sem Arthritis Rheum 2009.
Pathophysiology of Fibromyalgia

Central sensory
sensitisation Brain

Afferent activity from fast

(Aδ) & slow (C) fibres
from peripheral mechano
& nociceptors to dorsal
horn
Stimulus

Intense and repetitive Spinal cord

stimulation → peripheral
windup
Pathophysiology of Fibromyalgia
Normal descending
inhibitory tone from
brainstem to dorsal horn Brain

modulates afferent sensory

information (DNIC)
- reduced in FM due to
central 5HT & NA
dysfunction
→ Increased sensitivity of
nociceptive-specific Stimulus Spinal cord
neurons & wide dynamic
range neurons in the
dorsal horn
 Pathophysiology of Fibromyalgia

Transmission of usually non-painful sensations eg. movement

or light touch, via pain pathways in spinothalamic tract

Results in Allodynia
– where non-painful stimuli
are experienced as painful
Pathophysiology of Fibromyalgia
Amplification in pain processing
Pain pathway signals transmitted via
the thalamus to the somatosensory Brain

cortex where they are influenced by

emotional and cognitive centres

• spread of cerebral activation

• more widespread brain region activation
Spinal cord
• greater intrinsic connectivity between multiple Stimulus
brain networks
associated with pain perception and cognition
• Reduced connectivity between DMN & pain inhibitory centres

• Alterations in autonomic NS and neuroendocrine axis

• Changes in neurotransmitter profiles (reduced 5HT, NA, etc)
• Disruption of stage 4 nREM sleep
 Peripheral changes
Peripheral micro-inflammatory component of central sensitization
antidromic transmission along C fibres from dorsal horn

• Release of peripheral inflammatory neuropeptides & cytokines

• increased skin blood flow, vascular permeability and egress of PMLs
resulting in neurogenic inflammation
• Glial cell activation
• Modulation of this activity comes from pathways arising in midbrain
and brainstem via opioid and 5-HT/NA mechanisms – all abnormal in
FM

Small (A-δ and C) fibre abnormalities

• number, structure & function impairment in around 50% of patients
with FM
Littlejohn G, Guymer E. Sem Immunopath 2018
Oaklander AL et al. Pain. 2013; 154(11):2310–6
Uceyler N et al. Brain. 2013;136:1857-67
Giannocarro M et al. Muscle Nerve. 2014;49:757-9
 Neurogenic inflammation Increased
albumin and IgG
Structurally at
abnormal dermoepidermal
and reduced junction
C & A delta
fibres
Increased
stimulation
sensitivity in
nociceptive
terminals

Increased
mast cells
in skin Higher %
damaged/
degranulated
mast cells
Littlejohn, Nature Rev Rheum 2015
Clinical Features of Fibromyalgia

≥ 3 months chronic widespread bodily pain

• Other variable (central sensitivity symptoms)
• Fatigue
• Stiffness
• Unrefreshing sleep
• Cognitive disturbances
• memory & attention
• Emotional distress
• Paraesthesiae / dysaesthesiae
Every patient has a different
and fluctuating clinical
spectrum
Chronic, fluctuating
disease course, but not
dangerous and can
improve

• Autonomic dysfunction
 Amplified sensations in FM
• Pain
• Dysaesthesia / paraesthesia
• Tinnitus
• Bowel and bladder sensations
• Dizziness & palpitations
• Noise / light / odours
• Sensitivities to chemicals
• Side effects with drugs
 Fibromyalgia
Associated Conditions

• Depression • TMJ disorder

• Anxiety • Chronic sinus pain
• Headache • Multiple chemical sensitivities
• Irritable bowel • Pelvic pain
• Irritable bladder • Vulvodynia
• Interstitial cystitis • Restless legs syndrome
 Chronic
Fatigue
Syndrome

Irritable Bowel Regional Pain

Syndrome Syndrome

Fibromyalgia

Irritable Multiple
Bladder Chemical
Syndrome Sensitivities

Restless Legs
Syndrome

Adapted from Yunus

 Diagnosis of Fibromyalgia
History
• Clinical features suggestive of increased central sensitivity

Physical examination

• Evidence for all causes of chronic pain

• Often see widespread musculoskeletal tenderness
• Other features such as dermatographia suggestive of
peripheral sensitivity and microinflammation
• Sometimes postural hypotension or tachycardia
 Investigation FBE
ESR & CRP
Renal & liver function
Calcium and phosphate
• No “diagnostic” test for Thyroid function
fibromyalgia CK
• Many mimics and Vitamin D
associated conditions
• Rational investigation of
fibromyalgia will depend Further investigation depending
on individual clinical on clinical features:
eg. ANA, RhF/CCP Abs, Imaging,
features Nerve conduction studies, Sleep
studies
ACR 2016 revised Fibromyalgia criteria
Wolfe, F. et al. Sem. Arth. Rheum. 46 (2016) 319-329

Extent of musculoskeletal pain

• Count of self-reported painful regions over
past week
Widespread Pain Index (WPI)
maximum score 19
ACR 2016 revised Fibromyalgia criteria
Wolfe, F. et al. Sem. Arth. Rheum. 46 (2016) 319-329

Burden of central
sensitivity symptoms
• Including fatigue, sleep disturbance,
cognitive problems, abdominal pain,
headache and depression

Symptom Severity Score (SSS)

maximum score 12
ACR 2016 revised fibromyalgia criteria
Wolfe, F. et al. Sem. Arth. Rheum. 46 (2016) 319-329

1. Widespread Pain Index (WPI) ≥ 7 and Symptom Severity

Scale (SSS) ≥ 5 or WPI 4 – 6 and SSS ≥ 9
2. Generalised Pain (in at least 4 of 5 regions) –not jaw,
chest or abdomen
3. Symptoms generally present for 3 months
4. A diagnosis of fibromyalgia is valid irrespective of other
diagnoses. A diagnosis of fibromyalgia does not exclude
the presence of other clinically important illnesses.
 Fibromyalgia Symptom Score
• The ACR 2016 criteria subscores (WPI and SSS) can be added to produce
the Fibromyalgia Symptom Score (FSS)

• This allows for an assessment of an individual’s current level of “fibromyalgia-

ness”, or central sensitivity, on a continuous scale

• 92-96% of individuals who meet fibromyalgia criteria have a FSS ≥ 12

• FSS helps track levels of sensitivity over time in individuals

• Can predict post-op pain medication use even in individuals without

fibromyalgia
Brummett et al. Anesthesiology. 2013
 Management of Fibromyalgia

• Variable results even from proven therapies

• Stress & social factors
• Tolerance

• Best results with a multidisciplinary approach to

management
• No single treatment targets all symptoms

• At least moderate reduction in pain levels results in

improvement in:
• sleep, depression, anxiety, function, quality of life, ability to work
 Management of Fibromyalgia

Multidisciplinary team NECESSARY:

Best co-ordinated by the GP

• Psychologist
• Exercise physiologist
• Physiotherapist
• Other
• Myotherapist, naturopath, acupuncturist, etc
• Medical specialists
Management of Fibromyalgia
Needs to be MULTIDISCIPLINARY
Education *essential include family members if appropriate
FM is not dangerous or degenerative
• Diagnosis
• Mechanisms
• Dimensions
• Management principles
• Outcome and expectations

Patient understanding → proactive, regain sense of control

→ accept responsibility → begin to self-manage
 Management of Fibromyalgia
Exercise
• Proven benefits with graded, aerobic exercise
• Walking, warm pool
• Start low and slow
• Build to 20min 3x per week

Cognitive Behavioural Therapy

• Proven benefit, best with tailored program
• Helps patients live with the pain
• Relaxation, pacing, goal setting, coping strategies
Daily
• Mindfulness, meditation, exercise and good sleep hygiene
Management of Fibromyalgia
Other non-pharmacological
• Massage
• Acupuncture
• Yoga
• Tai-chi etc
Repetitive transcranial magnetic stimulation (rTMS) or
theta-burst stimulation (TBS)
• Overseas pilot data only
• Currently being trialed in Australia
Management of Fibromyalgia

Address other medical issues

• Concomitant illnesses
• Peripheral pain conditions, mood disorders, sleep disorders,
inflammatory disease
• Other symptoms
Address social issues
• Relationships
• Home
• Work
• Economic problems
 Management of Fibromyalgia

Drugs
• aim to target specific mechanisms and symptoms
• Start with low doses and gradually build
• At best, partial responses, not all patients (30/50 rule)
• Remember to treat associated conditions
• Peripheral pain conditions
• Mood disorders
• Associated conditions
• Sleep disorders
Management of Fibromyalgia

Analgesics
• Paracetamol

• Tramadol or Tapentadol (NA reuptake inhibition)

• NSAIDs – sometimes, for peripheral pain generators

Management of Fibromyalgia
Opioids
• No evidence to support use of opioids in fibromyalgia
• Possible overactivity of endogenous opioid system
• opioid hyperalgesia – type effects in some patients
• Significant safety concerns
• Not recommended
Naltrexone
• Used in low doses in small trials with some evidence of benefit
• Possibly helps with hyperactive endogenous opioid system or
microglial cell activation
Management of Fibromyalgia

Serotonin and Noradrenaline modulators

• Raise serotonin and NA concentrations
• TCAs reduce pain, fatigue & improve sleep, overall
well-being No TGA approval for use in Fibromyalgia in Australia

• Dual 5HT & NA reuptake inhibitors:

• Milnacipran only drug with Australian TGA approval for use in FM
DNIC +

• Helps pain, fatigue & global measures

• Duloxetine No TGA approval for use in Fibromyalgia in Australia

• Improves pain, fatigue & function

 Management of Fibromyalgia
Membrane stabilisers Pregabalin, gabapentin

• γ-aminobutyric acid (GABA) analogues

• Modulate Ca channels in hyper exited neurons by

binding to α-2-δ receptors → presynaptic
modulation of the release of excitatory Reduced

neurotransmitters→ membrane stabilisation

excitability

• α-2-δ ligands improve pain, sleep, fatigue and

general well-being in fibromyalgia
No TGA approval for use in Fibromyalgia in Australia
 Management of Fibromyalgia
Other drugs

• Ketamine: infusions can help with pain

• Cyclobenzaprine: some help with sleep – not available in

Australia

• Sodium Oxybate: safety concerns – not recommended

• Corticosteroids: no evidence for benefit, safety concerns – not

recommended
 Fibromyalgia - Summary
• Common, debilitating condition

• Widespread bodily pain & tenderness

• Central sensitisation of pain transmission neurons in the

dorsal horn → amplification of pain processing →
lowered pain threshold or allodynia

• Multidisciplinary management approach for best outcome

 Thank you

Any Questions?